Erros e incidentes de medicação na atenção primária: revisão integrativa / Errores e incidentes de medicación en la atención primaria: revisión integradora / Medication errors and incidents in primary care: integrative review

RESUMO Objetivo: Identificar, na literatura científica, publicações acerca dos erros de medicação e os incidentes relacionados, na atenção primária à saúde. Método: Realizou-se uma revisão integrativa da literatura nas bases de dados Medical Literature Analysis and Retrieval System on Line, Cumulative Index to Nursing and Allied Health Literature, Scientific Eletronic Library Online e Web of Science. Analisaram-se 17 artigos que atenderam aos critérios de inclusão. Para extração dos dados, fez-se a leitura, na íntegra, dos artigos selecionados. Resultados: dos 17 estudos analisados, sete (41,17%) foram indexados, tanto no PubMed, quanto no Medline; nove (52,94%) na Web of Science; um (5,9%) na base Scielo; e nenhum na Cinahl. Os estudos apontam fortes evidências na aplicação clínica, sendo que a maioria desses mostra que prescrições com medicamento incorreto, dose incorreta, interações medicamentosas e alergias medicamentosas foram as principais causas de erros com potencial para danos graves. Conclusão: Ainda é crescente o desenvolvimento de pesquisas que visem identificar estratégias e intervenções voltadas aos erros de medicação. Sabe-se que esses estudos fornecem subsídios para o aprimoramento das práticas, além de propiciar maior segurança no processo de medicação, a fim de reduzir os eventos adversos evitáveis.

RESUMEN Objetivo: identificar, en la literatura científica, publicaciones acerca de los errores de medicación y los incidentes relacionados, en la atención primaria a la salud. Método: se realizó una revisión integradora de la literatura en las bases de datos Medical Literature Analysis and Retrieval System on Line, Cumulative Index to Nursing and Allied Health Literature, Scientific Eletronic Library Online y Web of Science. Se analizaron 17 artículos que atendieron a los criterios de inclusión. Para la recolección de los datos, fue hecha la lectura, en su totalidad, de los artículos seleccionados. Resultados: de los 17 estudios analizados, siete (41,17%) fueron indexados, tanto en el PubMed, como en el Medline; nueve (52,94%) en la Web of Science; uno (5,9%) en la base Scielo; y ninguno en la Cinahl. Los estudios señalan fuertes evidencias en la aplicación clínica, siendo que la mayoría de ellos muestra que prescripciones con medicamento incorrecto, dosis incorrecta, interacciones y alergias a los fármacos fueron las principales causas de errores con potencial para daños graves. Conclusión: aún es creciente el desarrollo de investigaciones con el objetivo de identificar estrategias e intervenciones dirigidas a los errores de medicación. Sabemos que estos estudios aportan herramientas para el perfeccionamiento de las prácticas, además de ofrecer mayor seguridad en el proceso de medicación, a fin de reducir los eventos adversos evitables.

ABSTRACT Objective: To identify, in the scientific literature, publications on medication errors and related incidents in primary health care. Method: An integrative literature review was conducted in the databases Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, Scientific Electronic Library Online and Web of Science. Seventeen articles that met the inclusion criteria were analyzed. For data extraction, the selected articles were read in full. Results: Of the 17 studies analyzed, seven (41.17%) were indexed in both PubMed and Medline, nine (52.94%) in Web of Science, one (5.9%) in Scielo and none in Cinahl. The studies point to strong evidence in clinical application, most of these show that prescriptions with incorrect drugs, incorrect doses, drug interactions and drug allergies were the main causes of errors with potential for serious harms. Conclusion: The development of research aimed to identify strategies and interventions for medication errors is still growing. It is known that these studies provide subsidies for the improvement of practices, in addition to providing greater safety in the medication process, in order to reduce preventable adverse events.

Environmentally compatible bioconjugated gold nanoparticles as efficient contrast agents for inflammation-induced cancer imaging.

For many cancers, early detection is the key to improve survival and reduce the morbidity, which is associated with radical resections due to late diagnosis. Here, we describe the efficiency of primary antibody-conjugated gold nanoparticles (AuNPs) to specifically target chronic inflammatory processes, specially M2 macrophages, in tissue sections of ulcerative colitis (UC) and steatohepatitis in rats which may lead to colorectal cancer and liver carcinoma, respectively. In this study, we demonstrate that AuNPs synthesized by a simple, inexpensive, and environmentally compatible method can be easily conjugated with the antibodies anti-COX-2, anti-MIF, and Alexa Fluor® 488 (ALEXA) to perform immunofluorescence staining in inflamed tissues. Moreover, we showed that primary antibody-conjugated gold nanoparticles (AuNPs) can be used to target M2 macrophages by flow cytometry. We designed three immunofluorescence staining protocols of tissue section with AuNPs for 30 min and overnight incubation, as well as one flow cytometry protocol of M2 macrophage labeling with AuNPs for 30 min. Immunofluorescence and flow cytometry results suggest that conjugation was achieved by direct adsorption of antibodies on the AuNPs surface. When compared to the standard ALEXA protocol in immunofluorescence (IF) and flow cytometry (FC), our 30-min incubation protocol using AuNPs instead of ALEXA decreased from approximately 23 h to 5 h for IF and from 4 h to 1 h for FC, proving to be less laborious, which makes the method eligible for inflammation-induced cancer diagnostic.

Spherical neutral gold nanoparticles improve anti-inflammatory response, oxidative stress and fibrosis in alcohol-methamphetamine-induced liver injury in rats.

This study aimed to elucidate the anti-inflammatory, anti-oxidant and antifibrotic effects of gold nanoparticles (GNPs) in rats subjected to liver injury with ethanol and Methamphetamine (METH). The liver injury was induced by gavage administrations of 30% alcoholic solution (7 g/kg) once a day during 28 days, followed by METH (10 mg/kg) on the 20th and 28th days of treatment. GNPs treatment (724.96 µg/kg) during the ethanol and METH exposure was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis. Furthermore, there was a reduction in biochemical markers of liver damage and oxidative stress, and pro-inflammatory cytokines IL-1ß and TNF-α, compared to ethanol + METH group alone. A decrease of FGF, SOD-1 and GPx-1 expression was also observed. GNPs down-regulated the activity of Kupffer cells and hepatic stellate cells affecting the profile of their pro-inflammatory cytokines, oxidative stress and fibrosis through modulation of signaling pathways AKT/PI3K and MAPK in ethanol + METH-induced liver injury in a rat model.

Lipopolysaccharides and peptidoglycans modulating the interaction of Au naparticles with cell membranes models at the air-water interface.

Understanding the interactions between nanoparticles and biological surfaces is of great importance for many areas of nanomedicine and calls for detailed studies at the molecular level using simplified models of cellular membranes. In this paper, water-dispersed polyvinylpyrrolidonestabilized gold nanoparticles (AuNPs) were incorporated in floating monolayers of selected lipids at the air-water interface as cell membrane models. Surface pressure-area isotherms showed the condensation of glycoside-free lipid monolayers, suggesting their adsorption on the nanoparticle surface through the hydrophilic head groups. On the other hand, monolayers containing glycoside derivatives expanded upon AuNPs incorporation, pointing that the supramolecular structure formed should facilitate the incorporation of these nanoparticles in cellular membranes. These findings can be therefore correlated with the possible toxicity, microbicide and antitumorigenic effects of these nanoparticles in lipidic surfaces of erythrocyte and microbial membranes.

On the synergy between silver nanoparticles and doxycycline towards the inhibition of Staphylococcus aureus growth.

In a previous paper (RSC Adv., 2015, 5, 66886-66893), we showed that the combination of silver nanoparticles (NanoAg) with doxycycline (DO) culminated in an increased bactericidal activity towards E. coli. Herein we further investigated the metabolic changes that occurred on Staphylococcus aureus upon exposure to NanoAg with the help of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) coupled with multivariate data analysis. It has been discovered that the combination of DO with NanoAg produced metabolic changes in S. aureus that were not simply the overlap of the treatments with DO and NanoAg separately. Our results suggest that DO and NanoAg act synergistically to impede protein synthesis by the bacteria.

How the interaction of PVP-stabilized Ag nanoparticles with models of cellular membranes at the air-water interface is modulated by the monolayer composition.

The antimicrobial property of silver nanoparticles (AgNPs) is believed to be associated to their interaction with biointerfaces such as microbial cell membranes, encouraging research on the identification of membrane sites capable of AgNPs binding. Although significant progress has been made in that regard, the exact molecular mechanism of action is yet to be fully understood. In this study, AgNPs dispersed in aqueous media and stabilized with polyvinylpyrrolidone were incorporated in Langmuir monolayers of selected lipids that served as cell membrane models. Results from pressure-area isotherms, vibrational spectroscopy and Brewster angle microscopy revealed condensation of glycoside-free lipid monolayers, evidencing that the AgNPs interact mostly with the lipid hydrophilic head groups. In contrast, the monolayers of systems containing glycoside derivatives were found to expand upon AgNPs incorporation, indicating that the glycosidic compounds might facilitate the incorporation of these nanoparticles in cellular membranes. These data can be therefore correlated with the possible toxicity and microbicide effect of AgNPs in lipidic surfaces of mammalian and microbial membranes.

Apoptosis in human liver carcinoma caused by gold nanoparticles in combination with carvedilol is mediated via modulation of MAPK/Akt/mTOR pathway and EGFR/FAAD proteins.

In cancers, apoptosis signaling pathways and cell survival and growth pathways responsible for resistance to conventional treatments, such as Pi3K/Akt/mTOR and mitogen-activated protein kinase (MAPK) become dysregulated. Recently, alternative treatments to promote tumor cell death have become important. The present study reports on the antitumor and cytoprotective action of gold nanoparticles (GNPs) and carvedilol in combination and in isolated application. Apoptosis was analyzed by FITC/propidium iodide staining flow cytometry; caspase-3, caspase-8, Bcl-2 and MAPK/ERK activity by immunofluorescence microscopy; gene expression of proteins related to cell death as Akt, mTOR, EGFR, MDR1, survivin, FADD and Apaf, by the real-time PCR; and western blot analysis for MAPK/ERK, Akt and mTOR. Oxidative stress evaluation was performed by reduced glutathione (GSH) and malondialdehyde (MDA) levels. Intracellular GNPs targets were identified by transmission electron microscopy. After exposure to a combination of GNPs (6.25 µg/ml) and carvedilol (3 µM), death as promoted by apoptosis was detected using flow cytometry, for expression of pro-apoptotic proteins FADD, caspase-3, caspase-8 and sub-regulation of anti-apoptotic MAPK/ERK, Akt, mTOR, EGFR and MDR1 resistance. Non-tumor cell cytoprotection with GSH elevation and MDA reduction levels was detected. GNPs were identified within the cell near to the nucleus when combined with carvedilol. The combination of GNP and carvedilol promoted downregulation of anti-apoptotic and drug resistance genes, over-regulation of pro-apoptotic proteins in tumor cells, as well as cytoprotection of non-tumor cells with reduction of apoptosis and oxidative stress.

Anti-inflammatory, analgesic and anti-tumor properties of gold nanoparticles.

BACKGROUND: Gold nanoparticles (GNPs) are regarded as potential platforms for drug delivery. However, their interaction with live organisms must be understood prior to their utilization as drug carriers. The present study reports the anti-inflammatory, analgesic and anti-tumor effects of GNPs. The biodistribution of GNPs and their effect on various tissues have also been studied. METHODS: GNPs were synthesized through an environmentally friendly route and characterized with TEM and UV-vis. After HT-29 cells had been exposed to GNPs, apoptosis was assessed with Annexin V and propidium iodide staining and caspase-3 activity determined with a confocal laser scanning microscope. GNPs were administrated to male and female Swiss mice for posterior assessment of their anti-inflammatory and analgesic properties. The biodistribution of GNPs and their impact on tissues were studied with UV-vis and histopathological analysis, respectively. RESULTS: Cell apoptosis was observed in a dose-dependent manner for GNPs concentrations ranging from 40µg/mL to 80µg/mL (p<0.05). The best anti-inflammatory activity was observed at the dose of 1500µg/kg, which caused a reduction of 49.3% in leukocyte migration. GNPs showed peripheral analgesia at the dose of 1500µg/kg and have been found in liver, spleen, kidney and lungs. Histopathological examination revealed extravasation of red blood cells in lungs. CONCLUSION: The study draws attention to gold nanoparticles as a resource for technological innovation in the anti-inflammatory, analgesic and anti-tumor fields. GNPs have biological effects that deserve investigation to assess their full interaction with organic systems.